Thymoma Recurrence and its Predisposing Factors in Iranian Population: a Single Center Study

Background: Thymoma is relatively rare tumor. Prognosis and patients’ outcome vary across different studies. We aimed to study the predisposing factors causing tumor recurrence in thymoma patients. Materials and Methods: A total of 43 thymoma or thymic carcinoma patients treated at the National Institute of Tuberculosis and Lung Disease (NRITLD), Masih Daneshvari Hospital from September 2005 to January 2017 were evaluated. The primary endpoint was the progression free survival (PFS). The relation of predisposing factors to PFS was studied. Results: Median age was 55 years old. The mean of follow-up duration was 22.9 months. The most prevalent pathology was thymoma unspecified. Pure red cell aplasia (n=3, 6.9%) was the most prevalent Para neoplastic syndrome. Most of the patients (n=23, 54%) were in stage III and IV Masaoka-Koga staging system. Disease progression was observed in 17 patients (39. 5%). Most recurrences occurred locally. None of demographic characteristics differed between patients who experienced disease recurrence and those who did not. After univariate and multivariate analysis, predisposing factor for disease progression was only Masaoka-Koga stage (P-value=0.015 and 0.031 respectively). Conclusion: In this study, among different probable predisposing factors, only Masaoka-Koga stage had significant effect on disease recurrence. Large case-control studies may be required for better evaluation of risk factors.


INTRODUCTION
Primary thymus tumors-thymoma -are rare neoplasms originating from epithelial cells (1). Thymoma is a slowgrowing tumor and prognosis is very good if diagnosed in early stages. It is known as the most common mediastinal tumor (2). Annual incidence of thymoma is 1.3-3.  (4). Thus, thymus malignancies are commonly associated with abnormality of adaptive immunity and autoimmune disorders such as myasthenia gravis, pure red cell aplasia, or hypogammaglobulinemia (5).
Surgical resection is the primary treatment of thymoma but in unrespectable/inoperable cases, chemotherapy, targeted therapy, and radiation therapy may be considered. Thymoma recurrence is rare and varies according to different studies (6). Some of probable risk TANAFFOS factors for recurrence are: disease stage (7), histology (8), incomplete surgical resection of primary tumor (9) and tumor size (10).
As we know, thymoma predisposing factors are relatively unclear and vary from one study to another.
Therefore, we aimed to study our institute experiences over 12 years in thymoma patients' population and assess their outcome and probable disease progression risk factors. Most common histologic subtypes were unspecified thymoma (n=17, 39.5).     Stage is the only statistically significant in association with PFS.
Ahmad et al (29) claimed that female patients had worse prognosis and higher recurrence rate in comparison to men, but in most studies and also in current study equal gender association with prognosis in thymoma was observed (9,28,30).
Multiple classification systems for thymoma have been defined (28), but currently most of clinicians prefer the  (44). Some investigations reported long-term survival improvement after re-resection with recurrence (45), but other studies did not show that (46). In our opinion it seems that reoperation may be recommended for Thymoma relapse whenever complete resection is possible.
Similar to other studies (6), most of the recurrences in our series were local.
There are not many articles focusing on association between smoking status and Thymoma outcomes. Similar to our study, another investigation (47) found no relation between smoking habit and Thymoma prognosis.
The risk of secondary malignancies may be increased in Thymoma patients. Some investigators believe that deregulation of immune system and also kind of treatment (especially radiotherapy) have crucial role in inducing secondary malignancies (48). In our series no secondary malignancy was observed.
Currently, some genetic and epigenetic alternations such as epidermal growth factor receptor amplification, HER2/neu over expression (49), and c-Kit (CD 117) (50) activating mutation has been considered in thymoma pathogenesis (28). Due to rarity of thymoma, genetic study is not performed in routine practice and further studies are needed to show their relation with treatment and prognosis.
The most important limitation of our study was the retrospective nature of study and varying classification systems which may cause significant bias.
In conclusion Masaoka-Koga stage is the most important predisposing factor for disease recurrence among other factors. Further studies with larger number of patient's cohort, uniform classification system and tumor molecular characteristics are needed to identify prognostic and predisposing factors to improve patient's survival.

Conflict of Interest
There is no conflict of interest to declare.